The goal of this work is to understand the replication cycle of murine leukemia viruses (MuLV's) and the mechanism of Fv-1 restriction, a naturally occurring cellular system which specifically inhibits the replication of certain MuLV's. The studies use a number of cell culture techniques for quantitation of virus replication. Defective variants of MuLV have been isolated. Biological techniques for the study of these variants have been developed, including a method for rescuing defective MuLV and a plaque assay for quantitating defective MuLV particles. These variants will be used for genetic studies on MuLV replication. Previous work from this laboratory has shown that tropic MuLV's possess nongenetic determinants which render them sensitive to Fv-1 restriction, and that these determinants can be donated to other viruses by phenotypic mixing. In an extension of this work, the defective variants discussed above were shown to donate tropism to a NB-tropic MuLV, which is normally insensitive to Fv-1 restriction. BIBLIOGRAPHIC REFERENCES: Rein, A., Kashmiri, S.V.S., Bassin, R.H., Gerwin, B.I. and Duran-Troise, G.: Studies on the mechanism of Fv-1 restriction: Properties of determinants specfiying viral tropism. In Animal Virology, D. Baltimore, A.S. Huang, and C. F. Fox, (eds.) ICN-UCLA Symposia on Molecular and Cellular Biology IV, 269-282, 1976. Duran-Troise, G., Bassin, R.H., Rein, A. and Gerwin, B.I.: Loss of Fv-1 restriction in BALB/3T3 cells following infection with a single N-tropic murine leukemia virus particle. Cell 10: 479-488, 1977.